ThioBridge™ Conjugation Technology

Proprietary ADC linker technology

Creates less heterogeneous ADCs with better stability

Suitable for virtually any antibody or payload

Abzena has developed its ThioBridge™ technology to efficiently conjugate drugs to antibodies to create less heterogeneous ADCs with better stability. The technology links drugs to the naturally occurring interchain disulfide bonds of antibodies. The disulfide bonds are first reduced but, unlike conjugation using maleimide chemistry, the bonds are re-bridged as part of the conjugation process thereby stabilising the tertiary structure of the antibody.

The ThioBridge™ conjugation process can be optimised to consistently produce an ADC with a very high (around 90%) conversion to an ADC with one drug attached across each of the four reduced disulfide bonds. This results in an ADC with an antibody-drug-ratio of four (DAR 4) without requiring any re-engineering of the antibody prior to conjugation.

Application of ThioBridge™

ThioBridge™ can be used to attach a range of payloads using either cleavable or non-cleavable linkers to an antibody or other targeting molecule with accessible disulfide bonds. The technology has been applied to a variety of antibodies with different targets and a range of different types of smaller targeting molecules, including antibody fragments.

Benefits of ThioBridge™

More homogeneous

The synthesis of ThioBridge™ ADCs is highly reproducible with excellent conversion to homogeneous DAR 4 conjugates. A ThioBridge™ brentuximab ADC that otherwise contained the same components as Adcetris® was produced and was shown to be primarily DAR 4 as opposed to the more heterogeneous Adcetris®.

Highly flexible

ThioBridge™ is compatible with a wide range of payloads including auristatins (MMAE, MMAF), maytansinoids and DNA alkylating agents.

Better in vivo

The homogeneity and stability advantages of ThioBridge™, as well as Abzena’s expertise and experience in developing effective ADC reagents, results in more efficacious ADCs in vivo. A ThioBridge™ trastuzumab MMAE ADC was compared to the marketed ADC, Kadcyla®. In in vivo studies, the ThioBridge™ ADC showed a significant reduction in tumour volume compared to Kadcyla® after a single dose.

Above: Mean tumour volume over time for and Kadycla® in a JIMT-1 xenograft model and ThioBridge® trastuzumab MMAE.

*ThioBridge is a registered trademark in Europe and North America.

Working with Abzena

Abzena has applied ThioBridge™ to produce better antibody drug conjugates (ADCs) using whole antibodies, novel antibody formats and antibody fragments and have access, via our partners, to a range of cytotoxic drugs with different mechanisms of action. We collaborate with a wide range of organisations from virtual companies through to big pharma, including many of the world’s top companies, as well as academic research groups from across the globe.

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